A formidable toolkit exists for manipulating protein expression at the transcriptional level, but the methods for the post-translational modulation of proteins are few and of limited utility. A small molecule that induces degradation of endogenous proteins would clearly be a tremendously useful tool for probing protein function and an exciting approach for chemotherapy. The challenge is to develop technology that is biocompatible and widely applicable. We have serendipitously discovered a moiety that when combined with a recognition element, induces degradation of the target protein. We propose to characterize this phenomenon and develop these novel tools for protein knockdown that will be invaluable in a broad array of biological and pharmaceutical applications.